Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study

Upper aerodigestive tract (UADT) carcinomas have a high and rapidly increasing incidence, particularly in industrialized countries. The identification of diagnostic and prognostic biomarkers remains a key objective in oncological research. However, conflicting data have been reported regarding Lipoc...

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Main Authors: Luca Cavalcanti, Silvia Francati, Giampiero Ferraguti, Francesca Fanfarillo, Daniele Peluso, Christian Barbato, Antonio Greco, Antonio Minni, Carla Petrella
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/7/506
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author Luca Cavalcanti
Silvia Francati
Giampiero Ferraguti
Francesca Fanfarillo
Daniele Peluso
Christian Barbato
Antonio Greco
Antonio Minni
Carla Petrella
author_facet Luca Cavalcanti
Silvia Francati
Giampiero Ferraguti
Francesca Fanfarillo
Daniele Peluso
Christian Barbato
Antonio Greco
Antonio Minni
Carla Petrella
author_sort Luca Cavalcanti
collection DOAJ
description Upper aerodigestive tract (UADT) carcinomas have a high and rapidly increasing incidence, particularly in industrialized countries. The identification of diagnostic and prognostic biomarkers remains a key objective in oncological research. However, conflicting data have been reported regarding Lipocalin-2 (LCN-2 or NGAL), Matrix Metalloproteinase-9 (MMP-9), and the MMP-9/NGAL complex in UADT carcinomas. For this reason, the primary aim of this study was to investigate the involvement and modulation of the LCN-2 system in UADT cancer by selecting patients at first diagnosis and excluding any pharmacological or interventional treatments that could act as confounding factors. In this clinical retrospective pilot study, we investigated <i>LCN-2</i> and <i>MMP-9</i> tissue gene expression, as well as circulating levels of LCN-2, MMP-9, and the MMP-9/NGAL complex. Our findings revealed a downregulation of <i>LCN-2</i> and an upregulation of <i>MMP-9</i> gene expression in tumor tissues compared to healthy counterparts. A similar trend was observed in circulating levels, with decreased LCN-2 and increased MMP-9 in cancer patients compared to healthy controls. Additionally, serum levels of the MMP-9/NGAL complex were significantly elevated in UADT cancer patients relative to controls. Our study suggests a potentially distinct role for the free form of LCN-2 and its conjugated form (MMP-9/NGAL complex) in UADT tumors. These findings not only provide new insights into the molecular mechanisms underlying tumor progression but also highlight the potential clinical relevance of these biomarkers. The differential expression patterns observed suggest that the LCN-2 and MMP-9/NGAL complex could serve as valuable tools for improving early diagnosis, monitoring disease progression, and potentially guiding therapeutic strategies. Further research is needed to validate their utility in clinical settings and to explore their prognostic and predictive value in personalized treatment approaches.
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spelling doaj-art-8def584fd5f4437aadddaae2d7f0d8732025-08-20T02:09:21ZengMDPI AGCells2073-44092025-03-0114750610.3390/cells14070506Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot StudyLuca Cavalcanti0Silvia Francati1Giampiero Ferraguti2Francesca Fanfarillo3Daniele Peluso4Christian Barbato5Antonio Greco6Antonio Minni7Carla Petrella8Department of Sensory Organs, Sapienza University of Rome, 00161 Roma, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Roma, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Roma, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Roma, ItalyPhD School of Applied Medical-Surgical Sciences, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Roma, ItalyInstitute of Biochemistry and Cell Biology (IBBC-CNR), 00161 Roma, ItalyDepartment of Sensory Organs, Sapienza University of Rome, 00161 Roma, ItalyDepartment of Sensory Organs, Sapienza University of Rome, 00161 Roma, ItalyInstitute of Biochemistry and Cell Biology (IBBC-CNR), 00161 Roma, ItalyUpper aerodigestive tract (UADT) carcinomas have a high and rapidly increasing incidence, particularly in industrialized countries. The identification of diagnostic and prognostic biomarkers remains a key objective in oncological research. However, conflicting data have been reported regarding Lipocalin-2 (LCN-2 or NGAL), Matrix Metalloproteinase-9 (MMP-9), and the MMP-9/NGAL complex in UADT carcinomas. For this reason, the primary aim of this study was to investigate the involvement and modulation of the LCN-2 system in UADT cancer by selecting patients at first diagnosis and excluding any pharmacological or interventional treatments that could act as confounding factors. In this clinical retrospective pilot study, we investigated <i>LCN-2</i> and <i>MMP-9</i> tissue gene expression, as well as circulating levels of LCN-2, MMP-9, and the MMP-9/NGAL complex. Our findings revealed a downregulation of <i>LCN-2</i> and an upregulation of <i>MMP-9</i> gene expression in tumor tissues compared to healthy counterparts. A similar trend was observed in circulating levels, with decreased LCN-2 and increased MMP-9 in cancer patients compared to healthy controls. Additionally, serum levels of the MMP-9/NGAL complex were significantly elevated in UADT cancer patients relative to controls. Our study suggests a potentially distinct role for the free form of LCN-2 and its conjugated form (MMP-9/NGAL complex) in UADT tumors. These findings not only provide new insights into the molecular mechanisms underlying tumor progression but also highlight the potential clinical relevance of these biomarkers. The differential expression patterns observed suggest that the LCN-2 and MMP-9/NGAL complex could serve as valuable tools for improving early diagnosis, monitoring disease progression, and potentially guiding therapeutic strategies. Further research is needed to validate their utility in clinical settings and to explore their prognostic and predictive value in personalized treatment approaches.https://www.mdpi.com/2073-4409/14/7/506lipocalin-2matrix metalloproteinase-9MMP-9/NGAL complexupper aerodigestive tract carcinomas
spellingShingle Luca Cavalcanti
Silvia Francati
Giampiero Ferraguti
Francesca Fanfarillo
Daniele Peluso
Christian Barbato
Antonio Greco
Antonio Minni
Carla Petrella
Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study
Cells
lipocalin-2
matrix metalloproteinase-9
MMP-9/NGAL complex
upper aerodigestive tract carcinomas
title Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study
title_full Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study
title_fullStr Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study
title_full_unstemmed Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study
title_short Lipocalin-2, Matrix Metalloproteinase-9, and MMP-9/NGAL Complex in Upper Aerodigestive Tract Carcinomas: A Pilot Study
title_sort lipocalin 2 matrix metalloproteinase 9 and mmp 9 ngal complex in upper aerodigestive tract carcinomas a pilot study
topic lipocalin-2
matrix metalloproteinase-9
MMP-9/NGAL complex
upper aerodigestive tract carcinomas
url https://www.mdpi.com/2073-4409/14/7/506
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